Project Summary Epidemic control of HIV is feasible but only if we substantially strengthen our primary prevention efforts in adolescents and adults at risk and ensure the development of next-generation prevention methods. While much progress has been made in expanding effective biomedical prevention and in complementary behavioral and structural approaches, new infections in some groups and geographies, including in the United States, are not declining but are on the rise. With the results of up to five efficacy trials of new prevention technologies expected in 2020/21, the prevention field will face difficult decisions, skeptical and overburdened implementation audiences, and questioning communities. Against this background, the HIV Research for Prevention Conference 2020 (HIVR4P 2020) will be the key global scientific convening to reflect on the state of HIV prevention, recalibrate priorities, and map out a workplan for the coming decade. The conference will critically assess the latest research results in vaccine development, monoclonal antibody interventions, PrEP and other ARV-based approaches, long-acting and depot formulations, other novel prevention modalities, and relevant implementation science. Taking place in Cape Town, South Africa, on 11 to 15 October 2020, HIVR4P 2020 will have an attendance of 1,400 delegates from more than 50 countries. South Africa continues to play a significant role in product development and testing in cooperation with the United States. Attending HIVR4P in Cape Town will thus offer delegates the opportunity to benefit from learning about the successes and challenges in this critical setting while engaging in a broad scientific and policy exchange between specialists from the U.S, Europe, Asia and other regions with their African peers. The specific aims of HIVR4P 2020 are to: 1. Convene the world?s experts in HIV prevention and related fields to advance scientific knowledge, present new research findings, and enhance global scientific and community collaborations; 2. Advance evidence-informed and human rights-based HIV prevention that is tailored to the needs of particularly at risk and vulnerable groups to reduce health disparities including: adolescents and young adults, women and girls in high-burden settings, displaced populations, men who have sex with men, prisoners and other incarcerated people, people who use drugs, sex workers, and transgender people; 3. Refine HIV prevention research agendas to reflect identified opportunities and knowledge gaps, including: next generation of HIV vaccines and bNAbs; smarter delivery systems for molecules, including longer- acting and multi-purpose technologies; challenges and opportunities of further PrEP roll-out ad long-term PrEP use; integrated sexually transmitted infections (STI) and HIV prevention within broader sexual and reproductive health approaches; HIV prevention in the context of changing patterns of opioid use; and integrated prevention agendas that cut across disease and risk areas. The scientific program will be structured along five thematic areas: Basic science; PrEP and ARV-based prevention; Vaccines and bNAbs clinical trials; Other prevention modalities and cross-cutting issues; and Applied and implementation science. Cross-cutting aspects will be highlighted in plenary talks that also connect the scientific tracks with community and leadership perspectives. The participation of young researchers, basic scientists and researchers in related fields will be strengthened by active solicitation of relevant science and the provision of specific financial support. Free remote access to conference presentations and posters and robust social media dissemination will ensure reach beyond those able to attend in person and join the discussions on site.